In diagnosis of diabetes, it is common that first, primary screening is conducted with a urine glucose test or a fasting blood glucose level test, and, if such tests are positive a glucose tolerance test is performed to make a definite diagnosis. In recent years, HbA1C or fructosamine in the blood may also be tested before a glucose tolerance test using glucose.
However, the hitherto known methods, such as a urine glucose test and a fasting blood glucose level test, have the problem of low sensitivity since they show negative results of urine glucose and normal blood glucose levels for many diabetic patients, and thus overlook many cases of diabetic patients. Accordingly, the hitherto known methods are insufficient from the standpoint of preventive medicine for the reason that they cannot determine a state in which diabetes has not yet developed, but that is in a stage before onset of diabetes. In addition, although the glucose tolerance test using glucose is an excellent test, side effects caused by administration of a large amount of glucose have been indicated. Additionally, this test requires subjects to be restrained for several hours, and for blood to be repeatedly collected. Because this therefore imposes a great physical burden on subjects, this test can only actually be carried out on a limited number of subjects. Further, the results of HbA1C or fructosamine cannot be known until the next hospital visit, thus posing the drawback of insufficient rapidity.
Diagnosis of diabetes type (insulin dependent or noninsulin-dependent), determination of therapeutic strategy, and tests for evaluating the effect of treatment for diabetes are hitherto performed by mainly measuring blood insulin concentration, c-peptide in the blood or urine, blood glucose level in the glucose tolerance test using glucose, or change in blood insulin concentration over time. As described above, however, since the glucose tolerance test using glucose imposes a great physical burden on subjects, it is not actually conducted often. The result of blood insulin concentration or c-peptide in the blood or urine cannot be known until the next hospital visit; therefore, the rapidity of such tests is insufficient.
Meanwhile, applying measurement of 13CO2 excreted in expired air as carbon dioxide after administration of 13C-labeled glucose, i.e., a labeled C-breath test, to diagnosis of diabetes has been proposed (see Patent Literature 1 to 3). More specifically, Patent Literature 1 discloses a method for diagnosing the presence or absence of diabetes and the type of diabetes (type 1 diabetes or type 2 diabetes) by performing a breath test using glucose in which the carbon at a specific position is replaced by 13C, and determining the degree of increase in 13CO2 concentration excreted in expired air. Patent Literature 2 and 3 discloses performing a breath test using 13C-labeled glucose as in Patent Literature 1 and diagnosing a diabetic patient, an insulin-resistant patient, or a impaired glucose tolerance patient by using, as an index, the ratio of 13C to 12C (13C/12C) in expired air that is lower than the ratio or a healthy subject, the ratio being calculated from the concentration of 13CO2 excreted in the expired air.
However, none of these documents disclose or suggest that glucose metabolism ability of a subject can be detected with high accuracy with a labeled-C-breath test using glucose, allowing not only the stage of a patient in whom diabetes has developed to be determined and monitored, but also a stage before onset of diabetes.
Patent Literature 4 discloses a method in which 2H-labeled glucose is administered to a subject, the total amount of denterated water (2H2O) in the subject is measured, and a value obtained by dividing the total amount of deuterated water (2H2O) by the amount of insulin or the area under the curve of insulin concentration (insulin AUC) is used as an index to determine insulin resistance in the subject. Parent Literature 5 discloses a method in which the product of the area under the curve of insulin concentration (insulin AUC) and the area under the curve of glucose concentration (glucose AUC) (“insulin AUC×glucose AUC”) is determined from the blood glucose level and insulin concentration measured after administration of a food for testing, and the obtained value is used as an index to determine insulin resistance in a subject.
As described above, these documents disclose that the area under the curve of insulin concentration (insulin AUC) is taken into consideration for evaluation of insulin resistance in a subject; however, none of these documents disclose or suggest that glucose metabolism ability of a subject can be detected with high accuracy with a labeled C-breath test using glucose, allowing not only a stage of a patient in whom diabetes has developed to be determined and monitored, but also a stage before onset of diabetes.